Statistics is an indispensible tool for evaluating treatment effects in clinical research. Due to the complexities of periodontal disease progression and data collection, statistical analyses for periodontal research have been a great challenge for both clinicians and statisticians. The aim of this article is to provide an overview of several basic, but important, statistical issues related to the evaluation of treatment effects and to clarify some common statistical misconceptions. Some of these issues are general, concerning many disciplines, and some are unique to periodontal research. We first discuss several statistical concepts that have sometimes been overlooked or misunderstood by periodontal researchers. For instance, decisions about whether to use the t-test or analysis of covariance, or whether to use parametric tests such as the t-test or its non-parametric counterpart, the Mann-Whitney U-test, have perplexed many periodontal researchers. We also describe more advanced methodological issues that have sometimes been overlooked by researchers. For instance, the phenomenon of regression to the mean is a fundamental issue to be considered when evaluating treatment effects, and collinearity amongst covariates is a conundrum that must be resolved when explaining and predicting treatment effects. Quick and easy solutions to these methodological and analytical issues are not always available in the literature, and careful statistical thinking is paramount when conducting useful and meaningful research.